Recent studies in a number of different laboratories indicate the dependence of hepatocarcinogenesis on continued liver cell necrosis induced by the carcinogen. The major objective of our work continues to be the elucidation of the biochemical mechanisms underlying this toxic cell death. It is presumed that the understanding of these mechanisms will lead to the development of specific ways to interfere with the sequence and, thereby, to prevent the development of liver tumors. The proposed studies center around the hypothesis that toxic cell death results from an alteration in calcium homeostasis related in turn to membrane injury produced by the interaction of the toxin and its target cell. Experiments to pursue the nature of this membrane injury both in vivo and in vitro are proposed.